This project aims to elucidate the mechanisms and control of ionic permeability through excitable membranes. Several questions are being examined. (1) How do ions permeate through membranes? What is the nature of the conducting units? (2) How does the conducting structures distinguish between various species of ions? That is, what are the determinants of ion selectivity? (3) Why does membrane permeability to ions change rapidly in response to changes of membrane voltage? What is the nature of the structures involved in "gating" ionic permeabilities? In this regard we are intensively studying "gating currents" which we think are associated with the molecular conformational changes that lead to opening and closing of the ionic channels. Most experiments involve the voltage clamp technique, applied to internally perfused squid axons.